Autologous bone-marrow transplantation: host effects of high-dose BCNU.

Thirty-five patients with solid tumors received 44 courses of bis-chlorethylnitrosourea (BCNU) at doses ranging between 600 and 1,400 mg/m2 with cryopreserved or fresh autologous bone-marrow support. Eight patients treated at 600 mg/m2 received no bone-marrow support for their first course of BCNU. Maximum follow-up was 25 months (median, four months). Myelosuppression was severe and dose related but was less prolonged in the marrow-supported groups (p = 0.01) and was not dose limiting. Myelosuppression-related toxicity of infection and hemorrhage occurred in 21 (47%) of 44 courses of treatment. Pulmonary toxicity occurred in seven of 35 patients; abnormal liver function occurred in 18 of 30 patients greater than one month from treatment; and central nervous system symptoms that may have been drug related occurred in six of 35 patients. There was no renal or cardiac toxicity. Except for myelosuppression, toxicity was not dose related. Treatment-related deaths included four with pulmonary toxicity, two with liver toxicity, sepsis in four, and gastrointestinal tract toxicity in one patient. We conclude that the limiting side effect of high-dose BCNU (greater than or equal to 600 mg/m2) is visceral toxicity; the extent of myelosuppression is shortened by the infusion of bone marrow, whether cryopreserved or fresh; and marked tumor regression can be achieved with high-dose BCNU.

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High-dose therapy and autologous bone marrow transplantation in patients with follicular lymphoma during first remission

Blood ◽

10.1182/blood.v88.7.2780.bloodjournal8872780 ◽

1996 ◽

Vol 88 (7) ◽

pp. 2780-2786 ◽

Cited By ~ 162

Author(s):

AS Freedman ◽

JG Gribben ◽

D Neuberg ◽

P Mauch ◽

RJ Soiffer ◽

...

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

Bone Marrow Transplantation ◽

Follicular Lymphoma ◽

Marrow Transplantation ◽

Autologous Bone Marrow Transplantation ◽

Autologous Bone Marrow ◽

High Dose ◽

Autologous Bone

We report the results of a study in previously untreated advanced stage patients with follicular lymphoma (FL) who underwent uniform induction chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) followed by myeloablative therapy and anti-B-cell monoclonal antibody purged autologous bone marrow transplantation (ABMT). Eighty-three patients with previously untreated, low-grade FL were enrolled. After CHOP induction, only 36% achieved complete remission (CR) and 77 patients underwent ABMT. Before BM harvest, 70 patients had a known t(14;18), as determined by polymerase chain reaction (PCR), and all remained PCR positive in the BM at harvest. After ABMT, the disease-free survival (DFS) and overall survival are estimated to be 63% and 89% at 3 years, respectively, with a median follow-up of 45 months. Patients whose BM was PCR negative after purging experienced significantly longer freedom from recurrence (FFR) than those whose BM remained PCR positive (P = .0006). Continued PCR negativity in follow-up BM samples was also strongly predictive of continued CR. This study suggests that a subset of patients with advanced FL may experience prolonged clinical and molecular remissions following high-dose ablative therapy, although longer follow-up will be necessary to determine potential impact on overall survival.

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Accelerated hyperfractionated total-lymphoid irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for refractory and relapsing patients with Hodgkin's disease.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.6.1062 ◽

1993 ◽

Vol 11 (6) ◽

pp. 1062-1070 ◽

Cited By ~ 105

Author(s):

J Yahalom ◽

S C Gulati ◽

M Toia ◽

P Maslak ◽

E G McCarron ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Standard Dose ◽

Autologous Bone Marrow Transplantation ◽

Autologous Bone Marrow ◽

High Dose Chemotherapy ◽

High Dose ◽

Total Lymphoid Irradiation ◽

Autologous Bone

PURPOSE To evaluate the feasibility and therapeutic effect of accelerated hyperfractionated total-lymphoid irradiation (TLI), high-dose chemotherapy, and autologous bone marrow transplantation (AuBMT) in patients with relapsing or chemotherapy-resistant Hodgkin's disease (HD). PATIENTS AND METHODS Forty-seven patients with HD who either relapsed after chemotherapy (n = 19), or failed to respond (n = 28) to at least two regimens of combination chemotherapy were studied. No patient received prior radiation therapy (RT). Treatment started with reinduction with standard-dose chemotherapy, followed by involved-field irradiation (15 Gy) to areas of relapsed or persistent disease and TLI (20.04 Gy given in 1.67 Gy fractions three times per day for 4 days). Subsequently, patients received etoposide and high-dose cyclophosphamide, followed by infusion of unpurged autologous bone marrow. All surviving patients had a minimum follow-up duration of 1 year. The median follow-up duration for survivors was 40+ months, and the maximum follow-up duration was 80+ months. RESULTS Of the 47 patients treated, eight (17%) died of toxicity during the peritransplant period. Twenty-nine of the remaining 39 assessable patients (74%) attained a complete response (CR), while 10 remained with residual disease and progressed early after AuBMT. Four of the CR patients (14%) relapsed and 25 patients remained alive and free of disease. The actuarial disease-free survival (DFS) rate for the entire group at 6.5 years was 50%. Patients who received the protocol for relapsing HD had a significantly better DFS rate (79%) compared with patients treated for continuous refractory disease (DFS, 33%; P < .03). CONCLUSION Previously unirradiated patients with relapsing or chemotherapy-resistant HD who have exhausted conventional chemotherapy may still respond to an aggressive therapeutic approach consisting of accelerated hyperfractionated TLI, high-dose chemotherapy, and AuBMT rescue. This program offers a potential for long-term DFS to approximately one half of patients who would otherwise have a dismal prognosis with standard-dose salvage therapy.

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High-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation in mantle-cell lymphoma: no evidence for long-term remission.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.1.13 ◽

1998 ◽

Vol 16 (1) ◽

pp. 13-18 ◽

Cited By ~ 142

Author(s):

A S Freedman ◽

D Neuberg ◽

J G Gribben ◽

P Mauch ◽

R J Soiffer ◽

...

Keyword(s):

Monoclonal Antibody ◽

Bone Marrow ◽

Cell Lymphoma ◽

Autologous Bone Marrow Transplantation ◽

Autologous Bone Marrow ◽

High Dose ◽

Mantle Cell ◽

First Remission ◽

Autologous Bone

PURPOSE The role for high-dose therapy and autologous stem-cell transplantation in mantle-cell lymphoma (MCL) is unknown. We retrospectively analyzed patients with chemosensitive disease who underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation (ABMT) for MCL in first remission, as well as following relapse from conventional therapy. PATIENTS AND METHODS Between August 1985 and April 1996, 28 patients underwent ABMT using a uniform ablative regimen with cyclophosphamide and total-body irradiation (TBI) and a bone marrow-purging regimen. Re-review of original tissue demonstrated that all patients had morphologic, phenotypic, and genotypic characteristics of MCL. MCL was the original diagnosis in 21 patients, whereas seven patients had a prior diagnosis of diffuse small cleaved-cell lymphoma. RESULTS Twenty patients received multiple regimens before ABMT, while eight underwent ABMT in first complete remission (CR)/partial remission (PR) following CHOP induction. At bone marrow harvest, only 18% of patients were in CR and overt BM infiltration was present in 57%. Following cyclophosphamide/TBI, no treatment-related deaths were seen. Nineteen of 28 patients have relapsed at a median time of 21 months (range, 3 to 70). Of eight patients transplanted in first CR/PR, five have relapsed. Nine patients are in continuous CR with a median follow-up time of 24 months (range, 10 to 135). Disease-free survival (DFS) and overall survival (OS) are estimated to be 31% and 62% at 4 years, respectively. CONCLUSION ABMT using cyclophosphamide/TBI conditioning may at best be effective in only a small fraction of patients with relapsed MCL. The lack of plateau with a median follow-up time of 24 months suggests cure may not be achievable. The role of this therapy in patients in first remission requires more study using better induction therapy to enhance the CR rate before ABMT.

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